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BIG PHYSICS, BIG QUESTIONS –

Clues to aspirin’s anti-cancer effects revealed

By Lisa Raffensperger

One of the world’s oldest medicines may hold the secret to a very contemporary problem&colon; preventing cancer. Exactly why salicylate shows such potential as an anti-cancer treatment remains unclear, but a new study in mice offers clues.

Salicylate, found in willow bark, has been a key ingredient in medicine cabinets for thousands of years – ancient Egyptian manuscripts describe it as a treatment for inflammation. In a modified form – aspirin – it remains a successful anti-inflammatory and analgesic. Recently, though, research has revealed a puzzling side-effect of taking aspirin&colon; the drug seems to lower a person’s chances of developing some forms of cancer.

Aspirin is rapidly broken down inside the body into salicylate, so to investigate aspirin’s unexpected side-effects Grahame Hardie at the University of Dundee, UK, applied salicylate to cultured human cells derived from the kidney. He found that the drug activated AMPK, an enzyme involved in cell growth and metabolism that has been found to play a role in cancer and diabetes.

“This is an ancient herbal remedy which has probably always been part of the human diet,” says Hardie. “But despite that we’re still finding out how it works.”

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Co-author Greg Steinberg of McMaster University in Hamilton, Ontario, Canada, then tested high doses of salicylate on various types of mice. He found that those engineered to lack AMPK did not experience the same metabolic effects from salicylate as seen in mice with AMPK.

Salicylate, in a form called salsalate, has also shown promise as a treatment for insulin-resistance and type 2 diabetes. Those effects, however, appear not to be governed by AMPK. When insulin-resistant mice lacking AMPK were given salicylate, they showed the same improvement in blood glucose levels as normal mice.

“That’s what makes aspirin so scientifically and clinically interesting,” says Chris Paraskeva at the University of Bristol, UK, who was not involved in the work. “It potentially works through a number of different pathways.”

The finding potentially separates aspirin’s pain-relieving effects from its cancer protection, paving the way for new anti-cancer drugs that have fewer side-effects than aspirin. The next step will be to test salicylate directly in mouse models of cancer, and to see whether AMPK remains important in mediating an anti-cancer effect.